Irena Bova

Is Impaired Cerebral Vasomotor Reactivity a Predictive Factor of Stroke in Asymptomatic Patients

BACKGROUND AND PURPOSE Identification of the subgroup of asymptomatic patients with severe internal carotid artery stenosis and high risk of stroke has important clinical implications. Cerebral vasomotor reactivity provides information regarding intracranial hemodynamic features and might have a prognostic value in predicting cerebrovascular ischemic events, especially in patients with carotid stenosis. The aim of our study was to assess the cerebral vasomotor reactivity in asymptomatic patients with carotid stenosis and evaluate its role in stroke occurrence. METHODS Cerebral vasomotor reactivity was assessed using transcranial Doppler ultrasonology and the Diamox test (intravenous administration of 1.0 g acetazolamide) in 44 asymptomatic patients with severe (> 70%) internal carotid artery stenosis. Patients were followed up prospectively (mean, 2 years). RESULTS Cerebral vasomotor reactivity was estimated as good (> 40% increase of blood flow velocity in the middle cerebral artery ipsilateral to the carotid stenosis after undergoing the Diamox test) in 23 patients; it was impaired in the other 21. During the follow-up period, the overall annual rate for ipsilateral stokes was 2.3%; it was 7.9% for all ischemic cerebral events. No strokes or transient ischemic attacks occurred in the former group, but there were 7 cerebral ischemic events (2 strokes [1 fatal] and 5 transient ischemic attacks) in the latter group. There was a statistically significant correlation between cerebral ischemic events and impaired cerebral vasomotor reactivity (P = .009). CONCLUSIONS The data of this preliminary study suggest an important role of impaired cerebral vasomotor reactivity in predicting ischemic cerebral events. Preventive vascular surgery might be considered in this high-risk subgroup of asymptomatic patients with severe carotid stenosis.

The A677V Methylenetetrahydrofolate Reductase Gene Polymorphism and Carotid Atherosclerosis

BACKGROUND AND PURPOSE The alanine/valine (A/V) polymorphism at codon 677 of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene correlates with elevated levels of plasma homocysteine and with an increased risk of atherosclerotic cardiovascular disease. Our study was designed to assess the frequency of the A and V alleles in patients with asymptomatic severe carotid artery stenosis (CAS) assessed by extracranial duplex examination in comparison with age- and sex-matched subjects without carotid atherosclerosis. METHODS Consecutive patients (n=48; 28 men, mean+/-SD age 67.1+/-11. 4 years) with asymptomatic severe (>75%) CAS were compared with subjects without CAS (n=26; 15 men, aged 61.2+/-11.5). The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. The chi(2) analysis and t test were used to compare the groups. RESULTS The frequency of V alleles was significantly higher in the CAS group (0.47) compared with control subjects (0.27, chi(2) test; OR 2.4 [95% CI 1.1 to 5.3]; P<0.02). CONCLUSIONS Our results indicate that the MTHFR A677V allele is significantly associated with severe CAS.

Interleukin‐6 as an early predictor for one‐year survival following an ischaemic stroke/transient ischaemic attack

Background Early biomarkers for survival in an acute ischaemic stroke/transient ischaemic attack might serve as a useful tool for the clinician. Several studies have highlighted the role of inflammatory biomarkers as an early signal for acute ischaemic stroke prognosis. Aims This study examines the potential advantage of using high-sensitivity interleukin-6 as a possible biomarker at the early stages of acute stroke for identifying patients at a high risk for 12-month mortality. Methods Inflammatory biomarkers and neurological scores were determined in 250 patients following mild to moderate acute ischaemic stroke within 24 h of hospital admission. Outcome data on mortality were collected after 12 months. The signal detection methodology was used to identify subgroups that were at a high risk for 12-month mortality. Results Twelve months following the event, 234 of the 250 stroke patients survived. Signal detection identified predictors that distinguished individuals likely to die from those with a better recovery prediction. Plasma interleukin-6 concentration emerged as the optimal predictor, with a cut point of 6·47pg/ml, χ2 (I, N = 250) = 20·5, P<0·001. Interleukin-6 above 6·47 pg/ml during the acute phase predicted subsequent non-survival (P = 0·006, odds ratio 8·0). Conclusions This study demonstrates the clinical potential of using high-sensitivity interleukin-6 as an early signal for acute ischaemic stroke survival and suggests a clear cut point for patients at a high risk who might benefit from closer clinical surveillance and/or administration of therapeutic interventions.

Leukoaraiosis Is a Chronic Atherosclerotic Disease

Background and Purpose. White matter changes (WMCs), or leukoaraiosis (LA), are associated with increased age, hypertension, diabetes mellitus, and history of stroke. Although several lines of evidence suggest a role of atherosclerosis in atherothrombotic vascular events, their involvement in LA remains to be determined. Our study examines this association in ischemic stroke patients. Methods. One hundred and seventy consecutive ischemic stroke or transient ischemic attack (TIA) patients were included. All patients underwent brain computed tomography (CT) with assessment of the extension and severity of WMCs, carotid arteries duplex scan with measurements of intima-media thickness (IMT) and plaques. Results. Seventy-two patients (42.4%) were found to have white matter lesions, of whom 28.8% had advanced LA. Mean IMT was significantly higher in patients with LA and with advanced LA (P = 0.002, P = 0.003, resp.). In addition, LA and LA severity were associated with existence of carotid plaque (P = 0.007, P = 0.004, resp.). In multivariate logistic regression analysis, including all vascular risk factors, LA was found to be associated with age and IMT. Conclusion. This study reinforces the tight association between LA and carotid atherosclerosis in ischemic stroke patients. We conclude that a chronic atherosclerotic disease underlies the pathophysiology of leukoaraiosis and its progression.

Erythrocyte aggregation as an early biomarker in patients with asymptomatic carotid stenosis

Background: Atherosclerosis is a chronic inflammatory disease. Design: We have evaluated the degree of erythrocyte aggregation (EA) as a microinflammatory biomarker in a cohort of hospital-based, neurologically asymptomatic outpatients. Methods: The degree of EA and carotid artery stenosis was evaluated in 510 individuals by using a simple slide test and image analysis. Results: Four hundred and sixteen individuals had minimal carotid stenosis (< 30%); 47 had mild to moderate stenosis (30–69%) and 47 had severe stenosis (>70%). A significant correlation was noted between the degree of carotid stenosis and the erythrocyte sedimentation rate (ESR), white blood cell count (WBCC) and fibrinogen (r=0.160, p=0.005;r=0.191, p=0.001 andr=0.126, p=0.026, respectively). The significant correlation was noted between the degree of carotid stenosis and EA (r=0.209, p < 0.001). The subjects with severe stenosis differed significantly from the other groups in their ESR, WBCC and EA. High sensitivity C-reactive protein (hs-CRP) concentrations did not discriminate between the presence and absence of significant carotid atherosclerotic disease. Conclusions: Inflammatory biomarkers such as ESR and the EA test are more sensitive than hs-CRP to the presence of a significant atherosclerotic carotid burden. These biomarkers might aid in the detection and quantification of microinflammation in individuals with carotid atherosclerosis.

Gender differences in the expression of erythrocyte aggregation in relation to Bβ-fibrinogen gene polymorphisms in apparently healthy individuals

An increased erythrocyte aggregation (EA) is associated with capillary slow flow, tissue hypoxemia and endothelial dysfunction. Fibrinogen is a major determinant in the formation of aggregated red blood cells. It has been suggested that the B beta-fibrinogen -455 G/A polymorphism is associated with erythrocyte hyperaggregability in men with coronary artery disease. The purpose of this study was to investigate the influence of the beta-fibrinogen -455 G/A polymorphism on erythrocyte aggregation in apparently healthy individuals. Plasma fibrinogen, red blood cell count, serum lipids, erythrocyte sedimentation rate, and the genotype of the B beta-fibrinogen -455 G/A polymorphism were examined in a cohort of 545 apparently healthy individuals and those with atherothrombotic risk factors. A whole blood erythrocyte aggregation test was performed by using a simple slide test and image analysis. In men, EA levels and plasma fibrinogen levels were significantly higher in subjects carrying the -455 A allele compared to subjects with the -455 GG genotype. This association did not exist in women carrying the fibrinogen -455 A allele. The -455 GA/AA men presented significantly higher correlation between the plasma fibrinogen concentrations and EA. This observation raises the prospect of possible change in the functional properties of the -455 GA/AA fibrinogen, enhancing its ability to induce EH. This study suggests that the B beta-fibrinogen -455 A allele is related to EH in men only. Putative mechanism could be hyperfibrinogenemia and a functional change in the fibrinogen molecule that alters its ability to interact with red blood cells and supports the aggregability of these cells.

Wide‐range C‐reactive protein efficacy in acute ischemic stroke patients

Objective –  To compare the recently introduced wide‐range C‐reactive protein (wr‐CRP) with the widely used high‐sensitivity Behring Dade method (hs‐CRP) in acute stroke/transient ischemic attack (TIA) patients.